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Looking for participantsPhase1/Phase2

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer

Sponsor: BioNTech SE

NCT ID: NCT06827236

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
BNT323 (drug), BNT327 (drug)
How long the study runs
Study runs about 52 months (dates as stated)
About the drug or intervention
BNT323 — drug: Intravenous infusion · BNT327 — drug: Intravenous infusion
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
380
Started
2025-04-23
Last checked
2026-09

Plain English Summary

What is this study?

  • • Testing a new treatment for locally advanced breast cancer
  • • Phase1/Phase2 - 380 participants
  • • This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC)

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with locally advanced breast cancer

Where?

  • • Cambridge - Addenbrooke s Hospital
  • • Cardiff - Velindre Cancer Centre
  • • Leeds - St James's University Hospital
  • • London - Royal Free Hospital
  • • +3 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

This is a Phase I/II, multi-site, open-label, two-part study designed to evaluate the efficacy, safety, optimized dose and contribution of components of BNT323 (also known as trastuzumab pamirtecan and DB-1303) in combination with BNT327 (also known as pumitamig and PM8002) in participants with hormone receptor-positive (HR+) or hormone receptor-negative (HR-), Human epidermal growth factor receptor (HER)2-positive, HER2-low (immunohistochemistry \[IHC\] 1+ or IHC 2+/in situ hybridization -), HER2-ultralow (IHC 0, with membrane staining) or HER2-null breast cancer (BC), or triple-negative breast cancer (TNBC).

More detail

The study consists of two parts: * Part 1 - Dose escalation: In this part of the study, participants with histologically confirmed, chemotherapy-pretreated advanced HR+, HER2-low or HER2-ultralow BC will receive BNT323 in combination with BNT327 (BNT323 + BNT327) in a dose escalation design. This will define the recommended Phase 2 dose (RP2D) for the BNT323 + BNT327 combination therapy. * Part 2 - Dose optimization and exploratory cohorts: This part of the study will be an expansion phase, aiming to evaluate the efficacy and safety of the optimal dose combination and providing a more robust comparison against the other treatments. It will start once the enrollment in Part 1 is completed and the sponsor in conjunction with the Safety Review Committee has assessed available Part 1 efficacy and safety data. Part 2 of the study will have four cohorts, i.e., Cohorts 1 (dose optimization cohort), and Cohorts 2, 3, and 4 (exploratory cohorts). Recruitment to Cohorts 2, 3, and 4 will begin with RP2D from Part 1 and in parallel to randomization in Cohort 1. Randomization is planned for Cohort 1 in Part 2, i.e., participants will be randomized in 2:2:1:1 ratio into one of the four arms (Arms 1-4). No randomization is planned for any other cohort in Part 2.

Locally Advanced Breast CancerUnresectable Breast CarcinomaMetastatic Breast Cancer

How this trial compares with your answers

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What we know so far

Condition· Matched your search
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Still need:

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Biomarkers mentioned

PD-L1

Who cannot take part

  • ✗Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose...
  • ✗Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially...
  • ✗Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I...
  • ✗Have received any of the following therapies or drugs prior to the initiation of the study:
  • ✗Participants who have received prior treatment with BNT323.
See the full criteria
Key Inclusion Criteria (applicable to all participants and all parts unless otherwise specified): * Have pathologically documented BC that: * Is locally advanced, unresectable or metastatic. * Has a confirmed HER2 status as determined by the local laboratory as standard of care testing prior to study screening (Part 1, Part 2 Cohorts 2 and 4) or the central laboratory (Part 2, Cohorts 1 and 3) from the most recently collected pre-randomization tumor sample. * Has a documented history of HER2 expression consistent with the subgroup definitions (i.e., HER2-low, HER2-ultralow, HER2-null, HER2-positive, or TNBC) as per current American Society of Clinical Oncology/College of American Pathologists guidelines. * Have measurable disease defined by RECIST v1.1. * Has left ventricular ejection fraction ≥55% by either echocardiography or multi-gated acquisition (scanning) within 28 days before randomization/enrollment. Key Exclusion Criteria: * Have history of small bowel obstruction requiring hospitalization within the past 3 months prior to the first dose of IMP. * Have an uncontrolled intercurrent illness that would limit compliance with study requirement or substantially increase risk of incurring adverse events. * Have clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to randomization/enrollment. * Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Had prior treatment with topoisomerase I inhibitors, including antibody-drug conjugates with topoisomerase I inhibitor payloads such as trastuzumab deruxtecan. * Have received any of the following therapies or drugs prior to the initiation of the study: * Participants who have received prior treatment with BNT323. * Participants who received prior treatment with a programmed death-ligand 1 (PD-L1) / vascular endothelial growth factor (VEGF) bispecific antibody. Note: Prior treatment with programmed death 1 (PD-1)/VEGF bispecific antibodies, PD-1/PD-L1 inhibitors or anti-VEGF therapies are permitted. * Have received other systemic immunostimulatory agents or immunosuppressive therapies (such as interferon-α, interleukin-2, or methotrexate) within 4 weeks prior to the initiation of study treatment or are within five half-lives of the treatment drug (whichever is longer). Exception: excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens). * Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 3 weeks prior to the initiation of study treatment. NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Where Is This Study? (7 UK sites)

Addenbrooke s Hospital

Cambridge CB2 0QQ, United Kingdom

Recruiting
Hospital R&D contact (matched)

Stephen Kelleher

cuh.research@nhs.net01223 348490

Velindre Cancer Centre

Cardiff CF14 2TL, United Kingdom

Recruiting
Hospital R&D contact (matched)

Sarah Townsend

Velindre.R&Doffice@wales.nhs.uk02920 196165

St James's University Hospital

Leeds LS9 7TF, United Kingdom

Recruiting
Hospital R&D contact (matched)

R&I Team

leedsth-tr.researchfacilitation@nhs.net0113 2060469

Royal Free Hospital

London NW3 2QG, United Kingdom

Recruiting
Hospital R&D contact (matched)

Natasha Ajraam

rf-tr.randd@nhs.net020 375 82150

Royal Marsden Hospital

London SW36JJ, United Kingdom

Recruiting
Hospital R&D contact (matched)

Mark Brandon-Grove

research.development@rmh.nhs.uk020 3186 5416

The Christie Hospital

Manchester M20 4BX, United Kingdom

Recruiting
Hospital R&D contact (matched)

Research and Innovation Office

the-christie.ri@nhs.net---

Royal Marsden Hospital-Sutton

Sutton SM2 5PT, United Kingdom

Recruiting
Hospital R&D contact (matched)

Mark Brandon-Grove

research.development@rmh.nhs.uk020 3186 5416

How to Get in Touch

BioNTech clinical trials patient information

Sponsor contact

CONTACT

+49 6131 9084 patients@biontech.de
Data sourced from ClinicalTrials.gov · Last verified: 2026-09